Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome.

Fragile X syndrome (FXS) is a rare neurodevelopmental disorder caused by a CGG repeat expansion ≥ 200 repeats in 5' untranslated region of the FMR1 gene, leading to intellectual disability and cognitive difficulties, including in the domain of communication. A recent phase 2a clinical trial testing BPN14770, a phosphodiesterase 4D inhibitor, showed improved cognition in 30 adult males with FXS on drug relative to placebo. The initial study found significant improvements in clinical measures assessing cognition, language, and daily functioning in addition to marginal improvements in electroencephalography (EEG) results for the amplitude of the N1 event-related potential (ERP) component.

Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile x syndrome.

Fragile X syndrome (FXS) is a rare neurodevelopmental disorder caused by a CGG repeat expansion ≥ 200 repeats in 5' untranslated region of the FMR1 gene, leading to intellectual disability and cognitive difficulties, including in the domain of communication. A recent phase 2a clinical trial testing BPN14770, a phosphodiesterase 4D inhibitor, showed improved cognition in 30 adult males with FXS on drug relative to placebo. The initial study found significant improvements in clinical measures assessing cognition, language, and daily functioning in addition to marginal improvements in electroencephalography (EEG) results for the amplitude of the N1 event-related potential (ERP) component.

The comparison of expressed emotion of parents of individuals with fragile X syndrome to other intellectual disabilities.

Background: Parenting children and young adults with intellectual disabilities, including individuals with fragile X syndrome and Down syndrome, is challenging, joyful, and complicated. Exploring how parents talk about their children, and the quality of the parent/child relationship can provide insight into the home environment and interactional patterns of the family.

Method: Expressed emotion (EE) is a measurement of a family's emotional climate based on a parent or caregiver's report of warmth, emotional overinvolvement, hostility, and criticism.

Sensitivity of the NIH Toolbox to Detect Cognitive Change in Individuals With Intellectual and Developmental Disability.

Background And Objective: Individuals with intellectual disability (ID) experience protracted cognitive development compared with typical youth. Sensitive measurement of cognitive change in this population is a critical need for clinical trials and other intervention studies, but well-validated outcome measures are scarce. This study's aim was to evaluate the sensitivity of the NIH Toolbox Cognition Battery (NIHTB-CB) to detect developmental changes in groups with ID-fragile X syndrome (FXS), Down syndrome (DS), and other ID (OID)-and to provide further support for its use as an outcome measure for treatment trials.

Assessing processing speed among individuals with intellectual and developmental disabilities: A match-to-sample paradigm.

Speeded Matching (SpM) is a new processing speed match-to-sample test within the NIH Toolbox Cognitive Battery. It was designed to developmentally extend feasibility to younger children or individuals with intellectual or developmental disabilities (IDD). SpM reduces cognitive demands to tapping an identical match as opposed to judging and indicating whether two stimuli are identical.

A novel measure of matching categories for early development: Item creation and pilot feasibility study.

Background: Many cognitive tests assess a limited developmental span, making longitudinal measurement for trials aimed at improving cognition challenging. Tests targeting transitional skills, which integrate foundational abilities into complex schemas, may be amenable to assessment across a wide developmental span. Furthermore, tablet-based tests permit computer adaptive testing (CAT), which is psychometrically more efficient and could increase testing motivation, especially for children with developmental delays.

Effect of peri-operative crystalloid fluid rate on circulating hyaluronan in healthy dogs: A pilot study.

Hypervolemia can damage the endothelial glycocalyx, a key regulator of vascular permeability, coagulation and inflammation. A starting peri-operative crystalloid fluid rate of 5mL/kg/h is recommended for healthy dogs undergoing elective procedures but higher rates continue to be commonly used. This study aimed to determine if a higher starting perioperative fluid rate was associated with a greater increase in plasma concentrations of hyaluronan, a marker correlated with glycocalyx damage, in systemically healthy dogs undergoing elective surgical procedures.

Validation of the NIH Toolbox Cognitive Battery in intellectual disability.

Objective: To advance the science of cognitive outcome measurement for individuals with intellectual disability (ID), we established administration guidelines and evaluated the psychometric properties of the NIH-Toolbox Cognitive Battery (NIHTB-CB) for use in clinical research.

Methods: We assessed feasibility, test-retest reliability, and convergent validity of the NIHTB-CB (measuring executive function, processing speed, memory, and language) by assessing 242 individuals with fragile X syndrome (FXS), Down syndrome (DS), and other ID, ages 6 through 25 years, with retesting completed after 1 month. To facilitate accessibility and measurement accuracy, we developed accommodations and standard assessment guidelines, documented in an e-manual.

Human MMAA induces the release of inactive cofactor and restores methylmalonyl-CoA mutase activity through their complex formation.

Human mitochondrial methylmalonyl-CoA mutase (hMCM) is an isomerase that converts methylmalonyl-CoA to succinyl-CoA, a crucial step for the incorporation of some compounds derived from the diet into the central metabolism. hMCM employs highly reactive radicals from its cofactor (adenosylcobalamin, AdoCbl) to perform its reaction. Our previous work demonstrated that hMCM loses activity during catalysis and that the interaction with human MMAA (hMMAA), a GTPase protein, avoided this loss or restored hMCM activity.

Effects of ω-3 fatty acids on stereotypical behavior and social interactions in Wistar rats prenatally exposed to lipopolysaccarides.

Objective: Supplementation with ω-3 polyunsaturated fatty acids (PUFAs) can positively contribute to neurologic development, modulating inflammatory responses, promoting homeostasis, and having a positive effect on animal behaviors associated with mental disorders. The aim of this study was to evaluate behavioral and biochemical effects of ω-3 fatty acid supplementation in an animal model for mental disorders by prenatal maternal exposure to lipopolysaccardies (LPS) from the maternal immune activation.

Methods: Twelve pregnant Wistar rats were used.

Two translation initiation codons direct the expression of annexin VI 64kDa and 68kDa isoforms.

Annexin A6 is a multicompetent, multifunctional protein involved in several biological processes within and outside of the cell. Whereas HeLa cells express annexin A6 only as a 68/67-kDa doublet, indicating alternative splicing (Smith PD et al. (1994) Proc Natl Acad Sci USA 91, 2713-2717), the GMO2784 human fibroblast cell line expresses two additional isoforms at 64 and 58kDa.

Holocarboxylase synthetase acts as a biotin-independent transcriptional repressor interacting with HDAC1, HDAC2 and HDAC7.

In human cells, HCS catalyzes the biotinylation of biotin-dependent carboxylases and mediates the transcriptional control of genes involved in biotin metabolism through the activation of a cGMP-dependent signal transduction pathway. HCS also targets to the cell nucleus in association with lamin-B suggesting additional gene regulatory functions. Studies from our laboratory in Drosophila melanogaster showed that nuclear HCS is associated with heterochromatin bands enriched with the transcriptionally repressive mark histone 3 trimethylated at lysine 9.

Human phagosome processing of Mycobacterium tuberculosis antigens is modulated by interferon-γ and interleukin-10.

Intracellular pathogens, such as Mycobacterium tuberculosis, reside in the phagosomes of macrophages where antigenic processing is initiated. Mycobacterial antigen-MHC class II complexes are formed within the phagosome and are then trafficked to the cell surface. Interferon-γ (IFN-γ) and interleukin-10 (IL-10) influence the outcome of M.

Annexin VI is a mannose-6-phosphate-independent endocytic receptor for bovine β-glucuronidase.

Endocytosis and transport of bovine liver β-glucuronidase to lysosomes in human fibroblasts are mediated by two receptors: the well-characterized cation-independent mannose 6-phosphate receptor (IGF-II/Man6PR) and an IGF-II/Man6PR-independent receptor, which recognizes a Ser-Trp*-Ser sequence present on the ligand. The latter receptor was detergent extracted from bovine liver membranes and purified. LC/ESI-MS/MS analysis revealed that this endocytic receptor was annexin VI (AnxA6).

Amyloid-beta peptide binds to microtubule-associated protein 1B (MAP1B).

Extracellular and intraneuronal formation of amyloid-beta aggregates have been demonstrated to be involved in the pathogenesis of Alzheimer's disease. However, the precise mechanism of amyloid-beta neurotoxicity is not completely understood. Previous studies suggest that binding of amyloid-beta to a number of targets have deleterious effects on cellular functions.

Low temperatures in post-operative knee rehabilitation in rheumatoid arthritis patients.

Low temperatures were applied (in addition to kinesitherapy), in the form of injected air cooled to -75 C and CO2, to 22 patients (34 knees) recovering from total knee alloplasty or synovectomy. Each procedure lasted 5-7 minutes. The control group consisted o 22 patients (34 knees) treated with kinesitherapy only.

Surgical procedure in rheumatoid foot deformities: the experience for the Rheumatoorthopedics Department at the Institute of Rheumatology in Warsaw.

This article presents the principles governing surgical procedures in foot deformations operated at the Rheumatoorthopedics Department of the Institute of Rheumatology. The pathophysiology of foot deformities in the course of RA is discussed; indications and contraindications for surgical and conservative treatment are also given, as well as the principles for postoperative treatment.

History of rheumaorthopaedics in Poland.

Rheumaorthopaedics evolved as a division of orthopaedics in the sixties, when new methods of treatment of the RA were developed and introduced into clinical practice. A pioneer of rheumarthopaedics in Poland, also renowned in the world, was Prof. S.

Postoperative evaluation of plasma interleukin-6 concentration in patients after total hip arthroplasty.

Background. The aim of this study was to examine the circulating IL-6 in patients after orthopedic surgery, and the correlation between IL-6, body temperature and the level of postoperative pain. Material and methods.

The NC accreditation learning collaborative: partners enhancing local health department accreditation.

North Carolina (NC) is one of several states that have developed an accreditation system for local public health agencies. The NC Collaborative, composed of the NC Association of Local Health Directors, the NC Division of Public Health, and the NC Institute of Public Health, conducted several initiatives to enhance the NC accreditation system and contribute to the Multi-state Learning Collaborative. Two of these projects, benefits of accreditation and the Accreditation Road Map, are of potential national interest and can inform the proposed national, voluntary accreditation model.

Accreditation/Performance assessment on-site reviews in Michigan, Missouri, North Carolina, and Washington: implications for States and an evolving national model.

In 1988, the Committee for the Study of the Future of Public Health identified the core functions of assessment, policy development, and assurance as key roles of the public health governmental sector. Some states have developed accreditation or performance assessment programs to measure how state and/or local government carry out these functions. Several of these programs share a common "on-site review" component defined as a site-specific visit to assess, observe, interview, review, evaluate, and/or survey a local/state agency or program regarding its ability to meet a set of public health standards.

Pharmacokinetics of azithromycin and the combination of ivermectin and albendazole when administered alone and concurrently in healthy volunteers.

Azithromycin is a critical component of an integrated disease elimination program against trachoma. This study was conducted to evaluate whether azithromycin has a pharmacokinetic interaction with the combination of ivermectin and albendazole. Eighteen healthy volunteers were administered single doses of azithromycin, ivermectin/albendazole, and the combination of the three agents in random, crossover fashion.

78 kDa receptor for Man6P-independent lysosomal enzyme targeting: biosynthetic transport from endoplasmic reticulum to "high-density vesicles".

Recent work has shown that the cation-independent mannose 6-phosphate and the 78 kDa receptors for lysosomal enzyme targeting are located in different cell compartments. While the mannose 6-phosphate receptor is enriched in the Percoll fractions that contain Golgi apparatus, most of the 78 kDa receptor is localized in a heavy fraction at the bottom of the Percoll gradient. This report presents the biosynthetic transport of the 78 kDa receptor.

Shelf-price agreements: the next frontier in competitive bidding for coronary intervention supplies.

In an attempt to further reduce operating costs, in 2004 our institution embarked on a novel approach in which we defined the price to be paid for interventional cardiology supplies and challenged vendors to meet that price. The results suggest that this strategy can further reduce supply costs while maintaining collaborative relationships with vendors.